7f3p: Difference between revisions
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==Crystal structure of a nadp-dependent alcohol dehydrogenase mutant in apo form== | |||
<StructureSection load='7f3p' size='340' side='right'caption='[[7f3p]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7f3p]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermoanaerobacter_brockii Thermoanaerobacter brockii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F3P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F3P FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7f3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f3p OCA], [https://pdbe.org/7f3p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f3p RCSB], [https://www.ebi.ac.uk/pdbsum/7f3p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f3p ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ADH_THEBR ADH_THEBR] Alcohol dehydrogenase with a preference for medium chain secondary alcohols, such as 2-butanol and isopropanol. Has very low activity with primary alcohols, such as ethanol. Under physiological conditions, the enzyme reduces aldehydes and 2-ketones to produce secondary alcohols. Is also active with acetaldehyde and propionaldehyde. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein stability and evolvability influence each other. Although protein dynamics play essential roles in various catalytically important properties, their high flexibility and diversity makes it difficult to incorporate such properties into rational engineering. Therefore, how to unlock the potential evolvability in a user-friendly rational design process remains a challenge. In this endeavor, we describe a method for engineering an enantioselective alcohol dehydrogenase. It enables synthetically important substrate acceptance for 4-chlorophenyl pyridine-2-yl ketone, and perfect stereocontrol of both (S)- and (R)-configured products. Thermodynamic analysis unveiled the subtle interaction between enzyme stability and evolvability, while computational studies provided insights into the origin of selectivity and substrate recognition. Preparative-scale synthesis of the (S)-product (73 % yield; >99 % ee) was performed on a gram-scale. This proof-of-principle study demonstrates that interfaced proline residues can be rationally engineered to unlock evolvability and thus provide access to new biocatalysts with highly improved catalytic performance. | |||
Unlocking the Stereoselectivity and Substrate Acceptance of Enzymes: Proline-Induced Loop Engineering Test.,Qu G, Bi Y, Liu B, Li J, Han X, Liu W, Jiang Y, Qin Z, Sun Z Angew Chem Int Ed Engl. 2022 Jan 3;61(1):e202110793. doi: 10.1002/anie.202110793., Epub 2021 Nov 23. PMID:34658118<ref>PMID:34658118</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7f3p" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Thermoanaerobacter brockii]] | |||
[[Category: Bi Y]] | |||
[[Category: Gao J]] | |||
[[Category: Han X]] | |||
[[Category: Li Q]] | |||
[[Category: Liu WD]] | |||
[[Category: Qu G]] | |||
[[Category: Sun ZT]] | |||
[[Category: Wei HL]] | |||
Latest revision as of 20:09, 29 November 2023
Crystal structure of a nadp-dependent alcohol dehydrogenase mutant in apo formCrystal structure of a nadp-dependent alcohol dehydrogenase mutant in apo form
Structural highlights
FunctionADH_THEBR Alcohol dehydrogenase with a preference for medium chain secondary alcohols, such as 2-butanol and isopropanol. Has very low activity with primary alcohols, such as ethanol. Under physiological conditions, the enzyme reduces aldehydes and 2-ketones to produce secondary alcohols. Is also active with acetaldehyde and propionaldehyde. Publication Abstract from PubMedProtein stability and evolvability influence each other. Although protein dynamics play essential roles in various catalytically important properties, their high flexibility and diversity makes it difficult to incorporate such properties into rational engineering. Therefore, how to unlock the potential evolvability in a user-friendly rational design process remains a challenge. In this endeavor, we describe a method for engineering an enantioselective alcohol dehydrogenase. It enables synthetically important substrate acceptance for 4-chlorophenyl pyridine-2-yl ketone, and perfect stereocontrol of both (S)- and (R)-configured products. Thermodynamic analysis unveiled the subtle interaction between enzyme stability and evolvability, while computational studies provided insights into the origin of selectivity and substrate recognition. Preparative-scale synthesis of the (S)-product (73 % yield; >99 % ee) was performed on a gram-scale. This proof-of-principle study demonstrates that interfaced proline residues can be rationally engineered to unlock evolvability and thus provide access to new biocatalysts with highly improved catalytic performance. Unlocking the Stereoselectivity and Substrate Acceptance of Enzymes: Proline-Induced Loop Engineering Test.,Qu G, Bi Y, Liu B, Li J, Han X, Liu W, Jiang Y, Qin Z, Sun Z Angew Chem Int Ed Engl. 2022 Jan 3;61(1):e202110793. doi: 10.1002/anie.202110793., Epub 2021 Nov 23. PMID:34658118[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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